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Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor <jats:italic>\u03b2<\/jats:italic>-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10\u00a0mM carnosine, 10\u00a0mM <jats:italic>\u03b2<\/jats:italic>-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (<jats:italic>p<\/jats:italic>\u2009=\u20090.016 and <jats:italic>p<\/jats:italic>\u2009=\u20090.005). Treatment with 10\u00a0mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (<jats:italic>p<\/jats:italic>\u2009=\u20090.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (<jats:italic>p<\/jats:italic>\u2009=\u20090.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle.<\/jats:p>","DOI":"10.1007\/s00726-022-03230-9","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T12:30:00Z","timestamp":1673613000000},"page":"413-420","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells"],"prefix":"10.1007","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-8341","authenticated-orcid":false,"given":"Joseph J.","family":"Matthews","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-1053","authenticated-orcid":false,"given":"Mark D.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1915-6780","authenticated-orcid":false,"given":"Livia","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1122-5099","authenticated-orcid":false,"given":"Kirsty J.","family":"Elliott-Sale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-4169","authenticated-orcid":false,"given":"Craig","family":"Sale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"issue":"1","key":"3230_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep44492","volume":"7","author":"T Albrecht","year":"2017","unstructured":"Albrecht T, Schilperoort M, Zhang S, Braun JD, Qiu J, Rodriguez A, Pastene DO, Kr\u00e4mer BK, K\u00f6ppel H, Baelde H, de Heer E (2017) Carnosine attenuates the development of both type 2 diabetes and diabetic nephropathy in BTBR ob\/ob mice. 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MDT has received a British Council award to support a PhD studentship focused on research into carnosine (Grant number: 209524711). The remaining authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}